The candidate is a clinically trained veterinary oncologist, board- eligible in the American College of Veterinary Internal Medicine. His completed and planned Ph.D. course work is directed toward molecular pathology, genetics and transgenic animals in biomedical research. The candidate's long term interests lie in development and analysis of animal models of cancer biology, specifically metastasis, as a means to develop specific therapeutic protocols to slow or stop tumor spread. Breast cancer is the second leading cause of cancer death among women in the United States. Treatment of the primary cancer has made tremendous strides over the years, but unfortunately cancer progression leading to metastasis still occurs in many patients. The overall goal of this project is to analyze the intrinsic and extrinsic effects of genetically well defined transformed and non-transformed cells upon one another to determine how they affect tumor progression and metastasis. This goal will be achieved by employing transgenic mice that express cell - lineage specific markers and that overexpress growth factors, oncogenes, or proteinases in the mammary gland. Specifically, the aims are to document the degree of epithelial and mesenchymal clonality of hyperplastic and neoplastic mammary lesions induced by a growth factor or an oncogene by studying mice with transplantation-chimeric mammary glands; to define the range of action (autocrine versus paracrine) of a growth factor in transplantation chimeric glands; to characterize the phenotypic consequences of mammary epithelial-directed expression of transgenes encoding secreted proteinases or a proteinase receptor; and to identify the influence of proteinase expression upon mammary tumor progression. These studies will be conducted in the laboratories of the co-sponsors, Dr. Michael Gould in the Department of Human Oncology and Dr. Eric Sandgren in the Department of Pathobiological Sciences. Each is highly qualified in respective areas of mammary tumor biology and transgenic animal models of epithelial tumors. In addition, the University of Wisconsin-Madison provides an excellent environment in which to study cancer biology and metastasis. The outlined plan of training and the resources available provide the candidate with an outstanding opportunity to develop expertise in basic research to compliment his present expertise in clinical oncology.